micafungin and Cryptococcosis

The incidence of fungal infections has increased globally, and the introduction of the newer triazoles and echinocandin antifungals is a more-than-welcome and long overdue development. In this report, we review the clinical trials evaluating the therapeutic efficacy of these new antifungal agents and examine possible gaps in coverage. Voriconazole has become the primary treatment for most forms of invasive aspergillosis in a number of centers, posaconazole offers a broad antifungal spectrum, and echinocandins are fungicidal against most Candida species. Moreover, the new agents are active against some fungi that are resistant to amphotericin B, may have a role in the management of fever and neutropenia, and provide exciting options for combination antifungal therapy. However, significant questions remain, including the management of breakthrough infections and treatment failures and the efficacy of the new antifungal agents against less common fungi.

Topics: Antifungal Agents; Aspergillosis; Candidiasis; Caspofungin; Clinical Trials as Topic; Cryptococcosis; Echinocandins; Fever; Humans; Lipopeptides; Lipoproteins; Micafungin; Mycoses; Neutropenia; Peptides, Cyclic; Pyrimidines; Treatment Outcome; Triazoles; Voriconazole

Echinocandins are not active against basidiomycetous yeasts, such as Cryptococcus neoformans, Trichosporon, and Rhodotorula species, and zygomycosis. We present a patient with renal failure and candidemia, who developed a breakthrough fungal infection with cryptococcemia and cryptococcuria while receiving micafungin therapy.

Topics: Aged; Antifungal Agents; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Echinocandins; Fungemia; Humans; Lipopeptides; Male; Micafungin; Renal Insufficiency

Topics: Aged; Antifungal Agents; beta-Glucans; Cryptococcosis; Diagnostic Errors; Echinocandins; Fatal Outcome; Female; Humans; Immunocompromised Host; Lipopeptides; Micafungin; Pneumonia, Pneumocystis; Purpura Fulminans; Tomography, X-Ray Computed

The in vitro and in vivo antifungal activities of T-2307, a novel arylamidine, were evaluated and compared with those of fluconazole, voriconazole, micafungin, and amphotericin B. T-2307 exhibited broad-spectrum activity against clinically significant pathogens, including Candida species (MIC range, 0.00025 to 0.0078 microg/ml), Cryptococcus neoformans (MIC range, 0.0039 to 0.0625 microg/ml), and Aspergillus species (MIC range, 0.0156 to 4 microg/ml). Furthermore, T-2307 exhibited potent activity against fluconazole-resistant and fluconazole-susceptible-dose-dependent Candida albicans strains as well as against azole-susceptible strains. T-2307 exhibited fungicidal activity against some Candida and Aspergillus species and against Cryptococcus neoformans. In mouse models of disseminated candidiasis, cryptococcosis, and aspergillosis, the 50% effective doses of T-2307 were 0.00755, 0.117, and 0.391 mg.kg(-1).dose(-1), respectively. This agent was considerably more active than micafungin and amphotericin B against candidiasis and than amphotericin B against cryptococcosis, and its activity was comparable to the activities of micafungin and amphotericin B against aspergillosis. The results of preclinical in vitro and in vivo evaluations performed thus far indicate that T-2307 could represent a potent injectable agent for the treatment of candidiasis, cryptococcosis, and aspergillosis.

Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Benzamidines; Candida albicans; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Mycoses; Specific Pathogen-Free Organisms; Treatment Outcome